ATE361375T1 - METHODS FOR MODELING THE FUNCTION OF POLYPEPTIDE GALNAC TRANSFERASES AND SCREENING SUBSTANCES THEREOF - Google Patents

METHODS FOR MODELING THE FUNCTION OF POLYPEPTIDE GALNAC TRANSFERASES AND SCREENING SUBSTANCES THEREOF

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Publication number
ATE361375T1
ATE361375T1 AT01931464T AT01931464T ATE361375T1 AT E361375 T1 ATE361375 T1 AT E361375T1 AT 01931464 T AT01931464 T AT 01931464T AT 01931464 T AT01931464 T AT 01931464T AT E361375 T1 ATE361375 T1 AT E361375T1
Authority
AT
Austria
Prior art keywords
galnac
lectin domains
transferases
functions
inhibitors
Prior art date
Application number
AT01931464T
Other languages
German (de)
Inventor
Henrik Clausen
Helle Hassan
Celso Albuquerque Reis
Eric Paul Bennett
Original Assignee
Glycozym Aps
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glycozym Aps filed Critical Glycozym Aps
Application granted granted Critical
Publication of ATE361375T1 publication Critical patent/ATE361375T1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/005—Enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/91091—Glycosyltransferases (2.4)
    • G01N2333/91097—Hexosyltransferases (general) (2.4.1)
    • G01N2333/91102—Hexosyltransferases (general) (2.4.1) with definite EC number (2.4.1.-)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Physics & Mathematics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Attachment of O-glycans to proteins is controlled by a large family of homologous polypeptide GalNAc-transferases. Polypeptide GalNAc-transferases contain a C-terminal sequence with similarity to lectins. This invention discloses that the putative lectin domains of GalNAc-transferase isoforms, GalNAc-T4, -T7, -T2, and T3, are functional and recognize carbohydrates, glycopeptides, and peptides. These lectin domains have different binding specificities and modulate the functions of GalNAc-transferase isoforms differently. The lectin domains of GalNAc-T- and -T7 directs the glycopeptide specificities of these enzymes, while the lectin domains of GalNAc-T2 and -T3 directs broadening of donor substrate specificities to include UDP-Gal. Selective inhibitors of these functions that do not eliminate general catalytic activities are disclosed. Such inhibitors disclosed include free sugars, aryl-sugar derivatives, and glycopeptides. Inhibitors of GalNAc-transferase lectin domains are useful for altering the O-glycosylation capacity of cells, tissues, and organisms, and such agents may also interfere with other binding functions involved in intracellular sorting and secretion events.
AT01931464T 2000-05-11 2001-05-10 METHODS FOR MODELING THE FUNCTION OF POLYPEPTIDE GALNAC TRANSFERASES AND SCREENING SUBSTANCES THEREOF ATE361375T1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US20333100P 2000-05-11 2000-05-11

Publications (1)

Publication Number Publication Date
ATE361375T1 true ATE361375T1 (en) 2007-05-15

Family

ID=22753535

Family Applications (1)

Application Number Title Priority Date Filing Date
AT01931464T ATE361375T1 (en) 2000-05-11 2001-05-10 METHODS FOR MODELING THE FUNCTION OF POLYPEPTIDE GALNAC TRANSFERASES AND SCREENING SUBSTANCES THEREOF

Country Status (5)

Country Link
EP (1) EP1282725B1 (en)
AT (1) ATE361375T1 (en)
AU (1) AU2001258234A1 (en)
DE (1) DE60128218D1 (en)
WO (1) WO2001085215A2 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7338932B2 (en) 2000-05-11 2008-03-04 Glycozym Aps Methods of modulating functions of polypeptide GalNAc-transferases and of screening test substances to find agents herefor, pharmaceutical compositions comprising such agents and the use of such agents for preparing medicaments
DE60314658D1 (en) * 2002-11-08 2007-08-09 Glycozym Aps METHOD OF IDENTIFYING AGENTS PAINTING THE FUNCTIONS OF POLYPEPTIDE GALNAC TRANSFERASE MODULES, PHARMACEUTICAL COMPOSITIONS COMPRISING SUCH AGENTS, AND USE OF SUCH AGENTS FOR THE MANUFACTURE OF MEDICAMENTS
US20090142272A1 (en) * 2004-06-21 2009-06-04 Exelixis, Inc. Pfks as modifiers of the igfr pathway and methods of use
CA2977261A1 (en) 2006-10-04 2008-04-10 Kobenhavns Universitet Generation of a cancer-specific immune response toward muc1 and cancer specific muc1 antibodies
US20120214174A1 (en) * 2009-08-25 2012-08-23 Oncotherapy Science, Inc. Gene and polypeptide relating to breast cancer
WO2014024820A1 (en) * 2012-08-06 2014-02-13 塩野義製薬株式会社 Pharmaceutical composition for treating new chronic kidney disease and method for screening medicine for new chronic kidney disease
GB201406767D0 (en) 2014-04-15 2014-05-28 Cancer Rec Tech Ltd Humanized anti-Tn-MUC1 antibodies anf their conjugates
US11058675B2 (en) 2018-03-29 2021-07-13 Carnegie Mellon University Cell-based screening and compounds that modulate GaINAc-transferases

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5268364A (en) * 1991-12-12 1993-12-07 The Biomembrane Institute Method for inhibiting selectin-dependent adhesion of leukocytes and platelets by O-glycosylation modification
PL339773A1 (en) * 1997-09-05 2001-01-02 Glycim Oy Synthetic bivalent polylactose amines containing slex and method of using them
JP2002517474A (en) * 1998-06-10 2002-06-18 グリコデザイン インコーポレイテッド Directed combinatorial compound libraries and high-throughput assays for screening them

Also Published As

Publication number Publication date
DE60128218D1 (en) 2007-06-14
EP1282725B1 (en) 2007-05-02
EP1282725A2 (en) 2003-02-12
AU2001258234A1 (en) 2001-11-20
WO2001085215A9 (en) 2002-01-24
WO2001085215A3 (en) 2002-06-27
WO2001085215A2 (en) 2001-11-15

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